Comparison of two different oxygen saturation target ranges for automated oxygen control in preterm infants: a randomised cross-over trial.

OBJECTIVE: To compare the effect of peripheral oxygen saturation (SpO2) target range (TR) (either 91%-95% and 92%-96%) on the frequency and duration of hypoxic and hyperoxic episodes while on automated oxygen control using the OxyGenie controller. DESIGN: Randomised cross-over study. SETTING: Tertiary-level neonatal unit in the Netherlands. PATIENTS: Infants (n=27) with a median (IQR) gestational age of 27+0 (25+5-27+3) weeks and postnatal age of 16 (10-22) days, receiving invasive or non-invasive respiratory support. INTERVENTIONS: In both groups supplemental oxygen was titrated to a TR of 91%-95% (TRlow) or 92%-96% (TRhigh) by the OxyGenie controller (SLE6000 ventilator) for 24 hours each, in random sequence. After a switch in TR, a 1-hour washout period was applied to prevent carry-over bias. MAIN OUTCOME MEASURES: Frequency and duration of hypoxic (SpO2<80% for ≥1 s) and hyperoxic episodes (SpO2>98% for ≥1 s). RESULTS: Hypoxic episodes were less frequent when the higher range was targeted (TRhigh vs TRlow: 2.5 (0.7-6.2)/hour vs 2.4 (0.9-10.2)/hour, p=0.02), but hyperoxic episodes were more frequent (5.3 (1.8-12.3)/hour vs 2.9 (1.0-7.1)/hour, p<0.001). The duration of the out-of-range episodes was not significantly different (hypoxia: 4.7 (2.8-7.1) s vs 4.4 (3.7-6.5) s, p=0.67; hyperoxia: 4.3 (3.3-4.9) s vs 3.9 (2.8-5.5) s, p=0.89). CONCLUSION: Targeting a higher SpO2 TR with the OxyGenie controller reduced hypoxic episodes but increased hyperoxic episodes. This study highlights the feasibility of using an automated oxygen titration device to explore the effects of subtle TR adjustments on clinical outcomes in neonatal care. TRIAL REGISTRATION NUMBER: NL9662.

Comparison of two automated oxygen controllers in oxygen targeting in preterm infants during admission: an observational study.

OBJECTIVE: To compare the effect of two different automated oxygen control devices on time preterm infants spent in different oxygen saturation (SpO2) ranges during their entire stay in the neonatal intensive care unit (NICU). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Tertiary level neonatal unit in the Netherlands. PATIENTS: Preterm infants (OxyGenie 75 infants, CLiO2 111 infants) born at 24-29 weeks' gestation receiving at least 72 hours of respiratory support between October 2015 and November 2020. INTERVENTIONS: Inspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) between February 2019 and November 2020 and the CLiO2 controller (AVEA ventilator) between October 2015 and December 2018 as standard of care. MAIN OUTCOME MEASURES: Time spent within SpO2 target range (TR, 91-95% for either epoch) and other SpO2 ranges. RESULTS: Time spent within the SpO2 TR when receiving supplemental oxygen was higher during OxyGenie control (median 71.5 [IQR 64.6-77.0]% vs 51.3 [47.3-58.5]%, p<0.001). Infants under OxyGenie control spent less time in hypoxic and hyperoxic ranges (SpO2<80%: 0.7 [0.4-1.4]% vs 1.2 [0.7-2.3]%, p<0.001; SpO2>98%: 1.0 [0.5-2.4]% vs 4.0 [2.0-7.9]%, p<0.001). Both groups received a similar FiO2 (29.5 [28.0-33.2]% vs 29.6 [27.7-32.1]%, p=not significant). CONCLUSIONS: Oxygen saturation targeting was significantly different in the OxyGenie epoch in preterm infants, with less time in hypoxic and hyperoxic SpO2 ranges during their stay in the NICU.

Automated oxygen control for very preterm infants and neurodevelopmental outcome at 2 years-a retrospective cohort study.

Faster resolution of hypoxaemic or hyperoxaemic events in preterm infants may reduce long-term neurodevelopmental impairment. Automatic titration of inspiratory oxygen increases time within the oxygen saturation target range and may provide a more prompt response to hypoxic and hyperoxic events. We assessed routinely performed follow-up at 2 years of age after the implementation of automated oxygen control (AOC) as standard care and compared this with a historical cohort. Neurodevelopmental outcomes at 2 years of age were compared for infants born at 24-29 weeks gestational age before (2012-2015) and after (2015-2018) the implementation of AOC as standard of care. The primary outcome was a composite outcome of either mortality or severe neurodevelopmental impairment (NDI), and other outcomes assessed were mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and CBCL problem behaviour scores. A total of 289 infants were included in the pre-AOC epoch and 292 in the post-AOC epoch. Baseline characteristics were not significantly different. Fifty-one infants were lost to follow-up (pre-AOC 6.9% (20/289), post-implementation 10.6% (31/292). The composite outcome of mortality or severe NDI was observed in 17.9% pre-AOC (41/229) vs. 24.0% (47/196) post-AOC (p = 0.12). No significant differences were found for the secondary outcomes such as mild-moderate NDI, Bayley-III composite scores, cerebral palsy GMFCS, and problem behaviour scores, with the exception of parent-reported readmissions until the moment of follow-up which was less frequent post-AOC than pre-AOC. CONCLUSION: In this cohort study, the implementation of automated oxygen control in our NICU as standard of care for preterm infants led to no statistically significant difference in neurodevelopmental outcome at 2 years of age. WHAT IS KNOWN: • Neurodevelopmental outcome is linked to hypoxemia, hyperoxaemia and choice of SpO2 target range. • Automated titration of inspired oxygen may provide a faster resolution of hypoxaemic and hyperoxaemic events. WHAT IS NEW: • This cohort study did not find a significant difference in neurodevelopmental outcome at two years of age after implementing automated oxygen control as standard of care.

Clinical outcomes of preterm infants while using automated controllers during standard care: comparison of cohorts with different automated titration strategies.

OBJECTIVE: To compare short-term clinical outcome after using two different automated oxygen controllers (OxyGenie and CLiO2). DESIGN: Propensity score-matched retrospective observational study. SETTING: Tertiary-level neonatal unit in the Netherlands. PATIENTS: Preterm infants (OxyGenie n=121, CLiO2 n=121) born between 24+0-29+6 weeks of gestation. Median (IQR) gestational age in the OxyGenie cohort was 28+3 (26+3.5-29+0) vs 27+5 (26+5-28+3) in the CLiO2 cohort, respectively 42% and 46% of infants were male and mean (SD) birth weight was 1034 (266) g vs 1022 (242) g. INTERVENTIONS: Inspired oxygen was titrated by OxyGenie (SLE6000) or CLiO2 (AVEA) during respiratory support. MAIN OUTCOME MEASURES: Mortality, retinopathy of prematurity (ROP), bronchopulmonary dysplasia and necrotising enterocolitis. RESULTS: Fewer infants in the OxyGenie group received laser coagulation for ROP (1 infant vs 10; risk ratio 0.1 (95% CI 0.0 to 0.7); p=0.008), and infants stayed shorter in the neonatal intensive care unit (NICU) (28 (95% CI 15 to 42) vs 40 (95% CI 25 to 61) days; median difference 13.5 days (95% CI 8.5 to 19.5); p<0.001). Infants in the OxyGenie group had fewer days on continuous positive airway pressure (8.4 (95% CI 4.8 to 19.8) days vs 16.7 (95% CI 6.3 to 31.1); p<0.001) and a significantly shorter days on invasive ventilation (0 (95% CI 0 to 4.2) days vs 2.1 (95% CI 0 to 8.4); p=0.012). There were no statistically significant differences in all other morbidities. CONCLUSIONS: In this propensity score-matched retrospective study, the OxyGenie epoch was associated with less morbidity when compared with the CLiO2 epoch. There were significantly fewer infants that received treatment for ROP, received less intensive respiratory support and, although there were more supplemental oxygen days, the duration of stay in the NICU was shorter. A larger study will have to replicate these findings.

Comparing Descriptive Statistics for Retrospective Studies From One-per-Minute and One-per-Second Data.

Background: Large amounts of data are collected in neonatal intensive care units, which could be used for research. It is unclear whether these data, usually sampled at a lower frequency, are sufficient for retrospective studies. We investigated what to expect when using one-per-minute data for descriptive statistics. Methods: One-per-second inspiratory oxygen and saturation were processed to one-per-minute data and compared, on average, standard deviation, target range time, hypoxia, days of supplemental oxygen, and missing signal. Results: Outcomes calculated from data recordings (one-per-minute = 92, one-per-second = 92) showed very little to no difference. Sub analyses of recordings under 100 and 200 h showed no difference. Conclusion: In our study, descriptive statistics of one-per-minute data were comparable to one-per-second and could be used for retrospective analyses. Comparable routinely collected one-per-minute data could be used to develop algorithms or find associations, retrospectively.

Comparing pulse rate measurement in newborns using conventional and dry-electrode ECG monitors.

AIM: Heart rate (HR) is the most important parameter to evaluate newborns' clinical condition and to guide intervention during resuscitation at birth. The present study aims to compare the accuracy of NeoBeat dry-electrode ECG for HR measurement with conventional ECG and pulse oximetry (PO). METHODS: Newborns with a gestational age ≥32 weeks and/or birth weight ≥1.5 kg were included when HR evaluation was needed. HR was simultaneously measured for 10 min with NeoBeat, PO and conventional ECG. RESULTS: A total of 18 infants were included (median (IQR) gestational age 39 (36-39) weeks and birth weight 3 150 (2 288-3 859) grams). Mean (SD) duration until NeoBeat obtained a reliable signal was 2.5 (9.0) s versus 58.5 (171.0) s for PO. Mean difference between NeoBeat and ECG was 1.74 bpm (LoA -4.987-8.459 and correlation coefficient 0.98). Paired HR measurements over 30-s intervals revealed no significant difference between NeoBeat and ECG. The positive predictive value of a detected HR <100 bpm by NeoBeat compared with ECG was 54.84%, negative predictive value 99.99%, sensitivity 94.44%, specificity 99.99% and accuracy 99.85%. CONCLUSIONS: HR measurement with NeoBeat dry-electrode ECG at birth is reliable and accurate.

Comparison of two devices for automated oxygen control in preterm infants: a randomised crossover trial.

OBJECTIVE: To compare the effect of two different automated oxygen control devices on target range (TR) time and occurrence of hypoxaemic and hyperoxaemic episodes. DESIGN: Randomised cross-over study. SETTING: Tertiary level neonatal unit in the Netherlands. PATIENTS: Preterm infants (n=15) born between 24+0 and 29+6 days of gestation, receiving invasive or non-invasive respiratory support with oxygen saturation (SpO2) TR of 91%-95%. Median gestational age 26 weeks and 4 days (IQR 25 weeks 3 days-27 weeks 6 days) and postnatal age 19 (IQR 17-24) days. INTERVENTIONS: Inspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) and the CLiO2 controller (AVEA ventilator) for 24 hours each, in a random sequence, with the respiratory support mode kept constant. MAIN OUTCOME MEASURES: Time spent within set SpO2 TR (91%-95% with supplemental oxygen and 91%-100% without supplemental oxygen). RESULTS: Time spent within the SpO2 TR was higher during OxyGenie control (80.2 (72.6-82.4)% vs 68.5 (56.7-79.3)%, p<0.005). Less time was spent above TR while in supplemental oxygen (6.3 (5.1-9.9)% vs 15.9 (11.5-30.7)%, p<0.005) but more time spent below TR during OxyGenie control (14.7 (11.8%-17.2%) vs 9.3 (8.2-12.6)%, p<0.05). There was no significant difference in time with SpO2 <80% (0.5 (0.1-1.0)% vs 0.2 (0.1-0.4)%, p=0.061). Long-lasting SpO2 deviations occurred less frequently during OxyGenie control. CONCLUSIONS: The OxyGenie control algorithm was more effective in keeping the oxygen saturation within TR and preventing hyperoxaemia and equally effective in preventing hypoxaemia (SpO2 <80%), although at the cost of a small increase in mild hypoxaemia. TRIAL REGISTRY NUMBER: NCT03877198.

Automation of oxygen titration in preterm infants: Current evidence and future challenges.

For the preterm infant with respiratory insufficiency requiring supplemental oxygen, tight control of oxygen saturation (SpO2) is advocated, but difficult to achieve in practice. Automated control of oxygen delivery has emerged as a potential solution, with six control algorithms currently embedded in commercially-available respiratory support devices. To date, most clinical evaluations of these algorithms have been short-lived crossover studies, in which a benefit of automated over manual control of oxygen titration has been uniformly noted, along with a reduction in severe SpO2 deviations and need for manual FiO2 adjustments. A single non-randomised study has examined the effect of implementation of automated oxygen control with the CLiO2 algorithm as standard care for preterm infants; no clear benefits in relation to clinical outcomes were noted, although duration of mechanical ventilation was lessened. The results of randomised controlled trials are awaited. Beyond the gathering of evidence regarding a treatment effect, we contend that there is a need for a better understanding of the function of contemporary control algorithms under a range of clinical conditions, further exploration of techniques of adaptation to individualise algorithm performance, and a concerted effort to apply this technology in low resource settings in which the majority of preterm infants receive care. Attainment of these goals will be paramount in optimisation of oxygen therapy for preterm infants globally.

Cardiorespiratory monitoring in the delivery room using transcutaneous electromyography.

OBJECTIVE: To assess feasibility of transcutaneous electromyography of the diaphragm (dEMG) as a monitoring tool for vital signs and diaphragm activity in the delivery room (DR). DESIGN: Prospective observational study. SETTING: Delivery room. PATIENTS: Newborn infants requiring respiratory stabilisation after birth. INTERVENTIONS: In addition to pulse oximetry (PO) and ECG, dEMG was measured with skin electrodes for 30 min after birth. OUTCOME MEASURES: We assessed signal quality of dEMG and ECG recording, agreement between heart rate (HR) measured by dEMG and ECG or PO, time between sensor application and first HR read-out and agreement between respiratory rate (RR) measured with dEMG and ECG, compared with airway flow. Furthermore, we analysed peak, tonic and amplitude diaphragmatic activity from the dEMG-based respiratory waveform. RESULTS: Thirty-three infants (gestational age: 31.7±2.8 weeks, birth weight: 1525±661 g) were included.18%±14% and 22%±21% of dEMG and ECG data showed poor quality, respectively. Monitoring HR with dEMG was fast (median 10 (IQR 10-11) s) and accurate (intraclass correlation coefficient (ICC) 0.92 and 0.82 compared with ECG and PO, respectively). RR monitoring with dEMG showed moderate (ICC 0.49) and ECG low (ICC 0.25) agreement with airway flow. Diaphragm activity started high with a decreasing trend in the first 15 min and subsequent stabilisation. CONCLUSION: Monitoring vital signs with dEMG in the DR is feasible and fast. Diaphragm activity can be detected and described with dEMG, making dEMG promising for future DR studies.

Automated oxygen control in preterm infants, how does it work and what to expect: a narrative review.

BACKGROUND: Automated oxygen control systems are finding their way into contemporary ventilators for preterm infants, each with its own algorithm, strategy and effect. OBJECTIVE: To provide guidance to clinicians seeking to comprehend automated oxygen control and possibly introduce this technology in their practice. METHOD: A narrative review of the commercially available devices using different algorithms incorporating rule-based, proportional-integral-derivative and adaptive concepts are described and explained. An overview of how they work and, if available, the clinical effect is given. RESULTS: All algorithms have shown a beneficial effect on the proportion of time that oxygen saturation is within target range, and a decrease in hyperoxia and severe hypoxia. Automated oxygen control may also reduce the workload for bedside staff. There is concern that such devices could mask clinical deterioration, however this has not been reported to date. CONCLUSIONS: So far, trials involving different algorithms are heterogenous in design and no head-to-head comparisons have been made, making it difficult to differentiate which algorithm is most effective and what clinicians can expect from algorithms under certain conditions.